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Linda K McLoon, Krysta R Fitzpatrick, Samantha A McConnell; Effect of Treatment with Ciliary Neurotrophic Factor on Contractile Properties in Rabbit Extraocular Muscle. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1148. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Neurotrophic factors have the ability to alter extraocular muscle structure and function. Direct treatment with these factors can cause significant alteration in eye alignment. Previous microarray studies of extraocular muscles from human subjects with strabismus showed decreased ciliary neurotrophic factor (CNTF) gene expression compared to normal controls (Agarwal et al., 2016). The effect of CNTF treatment on contractile properties and force generation in adult rabbit superior rectus muscles were assessed.
Superior rectus muscles of adult rabbits were injected with 2µg CNTF in sterile saline once per day for 3 days while the contralateral superior rectus muscles received an equal volume of saline. One week after the first injection, the animals were euthanized, and both the CNTF- and placebo-treated superior rectus muscles were removed. Contractile properties and force generation were determined using in vitro physiological methods, and these data were compared to naïve control muscles.
Examined as force in grams or force normalized to muscle size calculated as mN/cm2, the CNTF-treated muscles showed decreased generated force compared to naïve control superior rectus muscles. Interestingly, the contralateral saline-injected muscles showed increased force compared to naïve control muscles. These differences were larger at higher stimulation frequencies. For all stimulation frequencies, time to 50% and 100% relaxation and overall rate of relaxation were significantly decreased in the CNTF-treated muscles compared to naïve control muscles. The maximum rate of contraction also decreased in the CNTF-treated muscles compared to naïve controls.
CNTF treatment of adult rabbit superior rectus muscles resulted in a decrease in force generation at all stimulation frequencies. In addition, the overall time and rate of muscle relaxation and rate of muscle contraction were decreased. These functional studies, combined with the evidence that muscles from human strabismus subjects had decreased CNTF gene expression support the hypothesis that alteration of CNTF signaling may be an effective approach for improving eye alignment as a treatment of strabismus. We propose that a combination of neurotrophic factors is likely needed to cause a significant change in eye alignment. Future studies will address the efficacy of this approach.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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